Photo of Daphne Haas-Kogan,  MD

Daphne Haas-Kogan, MD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-2291


dhaas-kogan@bwh.harvard.edu

Daphne Haas-Kogan, MD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Professor, Radiation Oncology, Harvard Medical School
  • Department Chair , Radiation Oncology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

My clinical and laboratory efforts center on the development of novel treatments for adult and pediatric brain tumors, with a focus on improving radiation therapy for these diseases. In studying genetic abnormalities of brain tumors and pediatric malignancies I aim to translate laboratory discoveries to the clinical treatment of cancer, hoping to help shape targeted therapies for adult and pediatric malignancies. Most recently we studied aberrant chromatin remodeling and activation of the phosphatidylinositol 3-kinase (PI3K) pathway as important mediators of pediatric high-grade glioma pathogenesis. We demonstrated that treatment with a novel, first-in-class dual inhibitor of histone deacetylases (HDACs) and PI3K (CUDC-907), in combination with radiotherapy evoked a potent cytotoxic response in pediatric high-grade gliomas and we identified a novel mechanism of action involving modulation of the DNA damage response by inhibiting radiation-induced DNA repair pathways, including homologous recombination and non-homologous end joining. The radiosensitizing effects of CUDC-907 were mediated by decreasing NFκB/Forkhead box M1 (FOXM1) recruitment to promoters of genes involved in the DNA damage response, and exogenous expression of NFκB/FOXM1 rescued CUDC-907-induced cytotoxicity. Together, these findings revealed CUDC-907 as a novel radiosensitizer with potent anti-tumor activity in pediatric high-grade gliomas and have provided the preclinical rationale for the combination of CUDC-907 with radiotherapy as a novel therapeutic strategy. More globally, this work identified NFκB and FOXM1, and their downstream transcriptional elements, as critical targets for new treatments for pediatric high-grade gliomas. This work has resulted in a multi-institutional clinical trial, testing dual histone deacetylases and PI3K inhibition for pediatric gliomas. My passion for patient care and scientific discovery are reflected in my election to Best Doctors in America soon after completing residency and every year since, along with my productive laboratory, continuously funded since completing training, including Program Project, SPORE, and R01 funding.

Publications

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  • Park JR, Kreissman SG, London WB, Naranjo A, Cohn SL, Hogarty MD, Tenney SC, Haas-Kogan D, Shaw PJ, Kraveka JM, Roberts SS, Geiger JD, Doski JJ, Voss SD, Maris JM, Grupp SA, Diller L. Effect of Tandem Autologous Stem Cell Transplant vs Single Transplant on Event-Free Survival in Patients With High-Risk Neuroblastoma: A Randomized Clinical Trial. JAMA 2019; 322:746-755. PubMed
  • Bhaskaran V, Nowicki MO, Idriss M, Jimenez MA, Lugli G, Hayes JL, Mahmoud AB, Zane RE, Passaro C, Ligon KL, Haas-Kogan D, Bronisz A, Godlewski J, Lawler SE, Chiocca EA, Peruzzi P. The functional synergism of microRNA clustering provides therapeutically relevant epigenetic interference in glioblastoma. Nat Commun 2019; 10:442. PubMed
  • de Blank P, Bandopadhayay P, Haas-Kogan D, Fouladi M, Fangusaro J. Management of pediatric low-grade glioma. Curr Opin Pediatr 2018. PubMed
  • Lamba N, Cagney DN, Brigell RH, Martin AM, Besse LA, Catalano PJ, Phillips JG, Pashtan IM, Bi WL, Claus EB, Golby AJ, Dunn IF, Smith TR, Tanguturi SK, Haas-Kogan DA, Alexander BM, Aizer AA. Neurosurgical Resection and Stereotactic Radiation Versus Stereotactic Radiation Alone in Patients with a Single or Solitary Brain Metastasis. World Neurosurg 2018. PubMed
  • Hwang WL, Wolfson RL, Niemierko A, Marcus KJ, DuBois SG, Haas-Kogan D. Clinical Impact of Tumor Mutational Burden in Neuroblastoma. Journal of the National Cancer Institute 2018. PubMed
  • Breneman JC, Donaldson SS, Constine L, Merchant T, Marcus K, Paulino AC, Followill D, Mahajan A, Laack N, Esiashvili N, Haas-Kogan D, Laurie F, Olch A, Ulin K, Hodgson D, Yock TI, Terezakis S, Krasin M, Panoff J, Chuba P, Hua CH, Hess CB, Houghton PJ, Wolden S, Buchsbaum J, Fitzgerald TJ, Kalapurakal JA. The Children's Oncology Group Radiation Oncology Discipline: 15 Years of Contributions to the Treatment of Childhood Cancer. Int J Radiat Oncol Biol Phys 2018; 101:860-874. PubMed
  • Pal S, Kozono D, Yang X, Fendler W, Fitts W, Ni J, Alberta JA, Zhao J, Liu KX, Bian J, Truffaux N, Weiss WA, Resnick AC, Bandopadhayay P, Ligon KL, Dubois SG, Mueller S, Chowdhury D, Haas-Kogan DA. Dual HDAC and PI3K inhibition abrogates NFκB- and FOXM1-mediated DNA damage response to radiosensitize pediatric high-grade gliomas. Cancer Res 2018. PubMed
  • Pinto N, DuBois SG, Marachelian A, Diede SJ, Taraseviciute A, Glade Bender JL, Tsao-Wei D, Groshen SG, Reid JM, Haas-Kogan DA, Reynolds CP, Kang MH, Irwin MS, Macy ME, Villablanca JG, Matthay KK, Park JR. Phase I study of vorinostat in combination with isotretinoin in patients with refractory/recurrent neuroblastoma: A new approaches to Neuroblastoma Therapy (NANT) trial. Pediatr Blood Cancer 2018. PubMed
  • Cagney DN, Martin AM, Catalano PJ, Reitman ZJ, Mezochow GA, Lee EQ, Wen PY, Weiss SE, Brown PD, Ahluwalia MS, Arvold ND, Tanguturi SK, Haas-Kogan DA, Alexander BM, Redig AJ, Aizer AA. Impact of pemetrexed on intracranial disease control and radiation necrosis in patients with brain metastases from non-small cell lung cancer receiving stereotactic radiation. Radiother Oncol 2018; 126:511-518. PubMed
  • Campbell K, Karski EE, Olow A, Edmondson DA, Kohlgruber AC, Coleman M, Haas-Kogan DA, Matthay KK, DuBois SG. Peripheral Blood Biomarkers Associated With Toxicity and Treatment Characteristics After (131)I- Metaiodobenzylguanidine Therapy in Patients With Neuroblastoma. Int J Radiat Oncol Biol Phys 2017; 99:468-475. PubMed
  • Marinoff AE, Ma C, Guo D, Snuderl M, Wright KD, Manley PE, Al-Sayegh H, Sinai CE, Ullrich NJ, Marcus K, Haas-Kogan D, Goumnerova L, London WB, Kieran MW, Chi SN, Fangusaro J, Bandopadhayay P. Rethinking childhood ependymoma: a retrospective, multi-center analysis reveals poor long-term overall survival. J. Neurooncol. 2017. PubMed
  • Cagney DN, Martin AM, Catalano PJ, Redig AJ, Lin NU, Lee EQ, Wen PY, Dunn IF, Bi WL, Weiss SE, Haas-Kogan DA, Alexander BM, Aizer AA. Incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy: A population-based study. 2017. PubMed
  • Martin AM, Cagney DN, Catalano PJ, Warren LE, Bellon JR, Punglia RS, Claus EB, Lee EQ, Wen PY, Haas-Kogan DA, Alexander BM, Lin NU, Aizer AA. Brain Metastases in Newly Diagnosed Breast Cancer: A Population-Based Study. JAMA Oncol 2017. PubMed
  • Li R, Polishchuk A, DuBois S, Hawkins R, Lee SW, Bagatell R, Shusterman S, Hill-Kayser C, Al-Sayegh H, Diller L, Haas-Kogan DA, Matthay KK, London WB, Marcus KJ. Patterns of Relapse in High-Risk Neuroblastoma Patients Treated With and Without Total Body Irradiation. Int J Radiat Oncol Biol Phys 2017; 97:270-277. PubMed
  • von Allmen D, Davidoff AM, London WB, Van Ryn C, Haas-Kogan DA, Kreissman SG, Khanna G, Rosen N, Park JR, La Quaglia MP. Impact of Extent of Resection on Local Control and Survival in Patients From the COG A3973 Study With High-Risk Neuroblastoma. J Clin Oncol 2016; 35:208-216. PubMed
  • Packer RJ, Pfister S, Bouffet E, Avery R, Bandopadhayay P, Bornhorst M, Bowers DC, Ellison D, Fangusaro J, Foreman N, Fouladi M, Gajjar A, Haas-Kogan D, Hawkins C, Ho CY, Hwang E, Jabado N, Kilburn LB, Lassaletta A, Ligon KL, Massimino M, Meeteren SV, Mueller S, Nicolaides T, Perilongo G, Tabori U, Vezina G, Warren K, Witt O, Zhu Y, Jones DT, Kieran M. Pediatric low-grade gliomas: implications of the biologic era. 2016. PubMed
  • Jones C, Karajannis MA, Jones DT, Kieran MW, Monje M, Baker SJ, Becher OJ, Cho YJ, Gupta N, Hawkins C, Hargrave D, Haas-Kogan DA, Jabado N, Li XN, Mueller S, Nicolaides T, Packer RJ, Persson AI, Phillips JJ, Simonds EF, Stafford JM, Tang Y, Pfister SM, Weiss WA. Pediatric high-grade glioma: biologically and clinically in need of new thinking. 2016. PubMed
  • Kamran SC, Berrington de Gonzalez A, Ng A, Haas-Kogan D, Viswanathan AN. Therapeutic radiation and the potential risk of second malignancies. Cancer 2016. PubMed
  • Bandopadhayay P, Ramkissoon LA, Jain P, Bergthold G, Wala J, Zeid R, Schumacher SE, Urbanski L, O'Rourke R, Gibson WJ, Pelton K, Ramkissoon SH, Han HJ, Zhu Y, Choudhari N, Silva A, Boucher K, Henn RE, Kang YJ, Knoff D, Paolella BR, Gladden-Young A, Varlet P, Pages M, Horowitz PM, Federation A, Malkin H, Tracy AA, Seepo S, Ducar M, Van Hummelen P, Santi M, Buccoliero AM, Scagnet M, Bowers DC, Giannini C, Puget S, Hawkins C, Tabori U, Klekner A, Bognar L, Burger PC, Eberhart C, Rodriguez FJ, Hill DA, Mueller S, Haas-Kogan DA, Phillips JJ, Santagata S, Stiles CD, Bradner JE, Jabado N, Goren A, Grill J, Ligon AH, Goumnerova L, Waanders AJ, Storm PB, Kieran MW, Ligon KL, Beroukhim R, Resnick AC. MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism. Nat Genet 2016; 48:273-82. PubMed
  • DuBois SG, Groshen S, Park JR, Haas-Kogan DA, Yang X, Geier E, Chen E, Giacomini K, Weiss B, Cohn SL, Granger MM, Yanik GA, Hawkins R, Courtier J, Jackson H, Goodarzian F, Shimada H, Czarnecki S, Tsao-Wei D, Villablanca JG, Marachelian A, Matthay KK. Phase I Study of Vorinostat as a Radiation Sensitizer with 131I-Metaiodobenzylguanidine (131I-MIBG) for Patients with Relapsed or Refractory Neuroblastoma. Clin Cancer Res 2015; 21:2715-21. PubMed
  • Polishchuk AL, Li R, Hill-Kayser C, Little A, Hawkins RA, Hamilton J, Lau M, Tran HC, Strahlendorf C, Lemons RS, Weinberg V, Matthay KK, DuBois SG, Marcus KJ, Bagatell R, Haas-Kogan DA. Likelihood of bone recurrence in prior sites of metastasis in patients with high-risk neuroblastoma. Int J Radiat Oncol Biol Phys 2014. PubMed
  • Huse JT, Wallace M, Aldape KD, Berger MS, Bettegowda C, Brat DJ, Cahill DP, Cloughesy T, Haas-Kogan DA, Marra M, Miller CR, Nelson SJ, Salama SR, Soffietti R, Wen PY, Yip S, Yen K, Costello JF, Chang S. Where are we now? And where are we going? A report from the Accelerate Brain Cancer Cure (ABC2) low-grade glioma research workshop. 2014; 16:173-8. PubMed
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